Discovery of 4-[(Z)-(4-bromophenyl)-(ethoxyimino)methyll-1′-[(2,4-dimethyl-3-pyridinyl)carbonyl]-4′-methyl-1,4′-bipiperidine N-oxide (SCH 351125):: An orally bioavailable human CCR5 antagonist for the treatment of HIV infection

被引：97

作者：

Palani, A

Shapiro, S

Clader, JW

Greenlee, WJ

Cox, K

Strizki, J

Endres, M

Baroudy, BM

机构：

[1] Schering Plough Corp, Inst Res, Chem Res, Kenilworth, NJ 07033 USA

[2] Schering Plough Corp, Inst Res, Drug Safety & Metab, Kenilworth, NJ 07033 USA

[3] Schering Plough Corp, Inst Res, Antiviral Res, Kenilworth, NJ 07033 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2001年 / 44卷 / 21期

关键词：

D O I：

10.1021/jm015526o

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Structure-activity studies on piperidino-piperidine 3 led to the discovery of SCH 351125 (1), a selective CCR5 antagonist with potent activity against RANTES binding (K-i = 2 nM), which possesses subnanomolar activity in blocking viral entry and has excellent antiviral potency versus a panel of primary HIV-1 viral isolates. Compound 1, which has good oral bioavailability in rats, dogs, and monkeys, is proposed as a potential therapeutic agent for the treatment of HIV-1 and has entered human clinical trials.

引用

页码：3339 / 3342

页数：4

共 16 条

[1]

BAROUDY BM, 2000, 7 C RETR OPP INF, pS17

[2] IDENTIFICATION OF RANTES, MIP-1-ALPHA, AND MIP-1-BETA AS THE MAJOR HIV-SUPPRESSIVE FACTORS PRODUCED BY CD8(+) T-CELLS [J].